A high-sensitive biosensor based on the GMR effect in the self-suspended grating (SSG) is proposed. The calculations demonstrated that the sensitivity of the proposed bio-sensor is near the theoretical limit compared with conventional GMR sensor. Based on the normalized Eigen-function of single layer homogenous grating, the resonance curves with respect to the different refractive indices of surrounding media are calculated, with which confirm the estimated sensitivity. In addition, the highly sensitive bio-sensor in the near and mid IR wavelength region is designed for liquids and gases detection respectively. The sensor can deliver the resolution over 1×10-5 in the near IR region in a large refractive index (1.3~1.7) range and provide better than 1×10-6 in mid IR region, which is enough for various bio-material detections. Therefore, the proposed bio-sensor is one or two order′s more sensitive than the conventional GMR sensors.